Abstract Systemic Inflammatory Response and organ failure (SIRS-CPB) is a major problem following cardiac surgery. The incidence increases with the amount of time on cardiopulmonary bypass. The mechanism is unknown. Our preliminary studies indicate that white cell activation by surface exposure during CPB is the cause. Our studies indicate that the white cell activation can be prevented by nitric oxide (NO) in the gas to the heart/lung machine. This research is designed to determine the cause of SIRS-CPB and prevention with NO.